Our medical policies are designed for informational purposes only and are not an authorization, or an explanation of benefits, or a contract. Receipt of benefits is subject to satisfaction of all terms and conditions of the coverage. Medical technology is constantly changing, and we reserve the right to review and update our policies periodically.

Description

Insulin potentiation therapy (IPT) uses insulin as an adjunctive agent to potentiate the effects of pharmacologic therapy in the treatment of cancer, infectious diseases, chronic degenerative disorders, and many other conditions.

The observation that some cancer cells may express a greater number of insulin receptors has been the basis of the hypothesis for IPT. The physiologic effects of insulin in IPT are thought to increase the permeability of cell membranes and facilitate increased intracellular absorption of pharmacologic agents. Theoretically, the increased absorption of a pharmacologic agent results in higher intracellular drug concentrations; lower dosage requirements could then reduce toxicity and adverse side effects. IPT was developed in the 1930s in Mexico by Donato Perez Garcia, Sr., MD. It is primarily used in the treatment of cancer, for which increasing the intracellular concentration and cytotoxic effects of chemotherapy agents while decreasing the adverse effects is thought to increase antitumoral activity and patient tolerance to treatment. There have been proponents of using IPT for other conditions as well, such as infectious diseases, chronic degenerative disorders, chronic fatigue syndrome and fibromyalgia.

For cancer patients, a hypoglycemic state is induced in the minutes prior to infusion with standard chemotherapy delivered at sub-therapeutic doses. During this time, the patient may experience moderate to severe symptoms of hypoglycemia, including sweating, lightheadedness, and nausea. The patient is infused with glucose solution after chemotherapy is initiated and hypoglycemia has been achieved. A typical treatment regimen consists of biweekly sessions for up to 9 weeks. (1)

Policy

Insulin potentiation therapy (IPT) is considered investigational.

Policy Guidelines

There is no specific CPT code describing IPT. The following series of CPT codes and HCPCS J codes are used to describe the various components of IPT. Some codes, such as the code for glucose testing, may be used more than once during a single session of IPT:

CPT codes

82948: Glucose; blood, reagent strip

90765: Intravenous infusion for therapy, prophylaxis, or diagnosis (specify substance or drug);initial; up to 1 hour

State or federal mandates (e.g., FEP) may dictate that all U.S. Food and Drug Administration (FDA)-approved devices, drugs, or biologics may not be considered investigational, and thus, these devises may be assessed only on the basis of their medical necessity.

Insulin potentiation therapy is typically offered in specialized clinics. Many locations through-out the United States offer insulin potentiation therapy. Further information is available online at:www.iptforcancer.com/index.php?md=13.

Rationale

This policy was originally created in 2005 and was regularly updated with searches of the MEDLINE database through 2009. The most recent literature search was performed for the period July 2009 through July 2010. Following is a summary of the key findings to date:

Insulin potentiation therapy (IPT) has been explored in a minority of physician practices since the 1930s. (2-4) However, there is only one randomized controlled trial on the effects of IPT in metastatic breast cancer. No studies have demonstrated that IPT is safe or effective in improving long-term health outcomes over standard or conventional pharmacologic treatment for any disease state. Also, it appears that this is not an area of active research.

The only randomized controlled clinical trial on IPT was published by Lasalvia-Prisco and colleagues who reported on 30 patients (3 groups of 10) randomly assigned to receive two 21-day courses of insulin with methotrexate (IPT), methotrexate alone, or insulin alone. (5) Patients had metastatic breast cancer that was resistant to fluorouracil, adriamycin, and cyclophosphamide, as well as hormone therapy (if they had a positive estrogen receptor status). The primary outcome assessed at 8 weeks after initiation of treatment was tumor response, using the response evaluation criteria in solid tumors (RECIST) system. The authors reported finding the RECIST status in the IPT group was 9 stable diseases and 1 progressive disease versus 3 stable and 7 progressive diseases in the methotrexate-only group and 2 stable and 8 progressive diseases in the insulin-only group (distribution of results: p less than .01, Chi-squared test). In addition, the IPT group had significantly lower increases in tumor size than the methotrexate-only and the insulin-only treatment groups (p less than .001). Toxicities were low in both the IPT group (only 1 World Health Organization [WHO] grade 1 mucositis) and the methotrexate-only group (WHO grade 1-2), as the individual methotrexate dosage of 2.5 mg/m² used in the study was lower than optimal. The authors suggest that these findings support the theory that the antitumoral effects of methotrexate were potentiated by the insulin. While this study may suggest that insulin enhances some biochemical event with the administration of chemotherapy in the short term, it does not report on any long-term effects or health outcomes.

A 2006 publication described preclinical safety and antitumor efficacy of insulin combined with irradiation. (6) Using the intestinal crypt regeneration assay, a delay in regrowth was noted when insulin therapy was combined with radiation. The need for larger preclinical assays was noted by the authors as a next step, before studies of possible clinical utility are conducted. Additional basic science research is currently being conducted on the role of insulin growth factors in cancer. (7)

No trials investigating the treatment of fibromyalgia, chronic fatigue syndrome, arthritis, or infections have been published or are currently recruiting subjects. (8)

Summary
Much of the information about insulin potentiation therapy (IPT) comes from short-term anecdotal reports. A single randomized controlled trial suggested that tumor progression can be affected by IPT at 8 weeks. No survival or longer term data are available. Therefore, further studies are needed to demonstrate whether improvements in health outcomes occur with the use of insulin potentiation therapy; IPT remains investigational.

Technology Assessments, Guidelines, and Position Statements
In 2008, the American Cancer Society released the following statement:

“Despite supporters' claims that insulin potentiation therapy has been well researched, no scientific studies that show safety and effectiveness have been published in available peer-reviewed journals. These claims cannot be verified.”
“There are also concerns about using lower doses of chemotherapy drugs. When chemotherapy drugs are tested in clinical trials, their effects are carefully monitored to learn which dose will best balance the need to kill cancer cells with the goal of keeping side effects at a tolerable level. There is no evidence that chemotherapy at a fraction of the recommended and tested dose can produce the same effect as the full dose if used with insulin.” (1)